Axitinib plus pembrolizumab combination therapy was found tolerable in patients with treatment-naïve advanced renal cell carcinoma (RCC), and it shows promising antitumor activity in this patient population, a study published in Lancet Oncology has shown.

Previous studies in which PD-1 checkpoint inhibitors were combined with VEGF-tyrosine kinase inhibitors (TKIs) has led to excess toxicity in patients, thereby halting further development. However, a team led by Michael B. Atkins, MD, of Georgetown-Lombardi Comprehensive Cancer Center in Washington, DC, sought to determine if combining axitinib, a more selective VEGF inhibitor, with the anti-PD-1 pembrolizumab could generate antitumor activity in patients with treatment-naïve advanced RCC.

The study was conducted in 2 phases: a dose-finding phase to estimate maximum tolerated dose, then a dose-expansion phase to further establish safety and determine preliminary efficacy. Eligibility patients were 18 years or older; had RCC, predominantly clear cell subtype, with the primary tumor resected and at least 1 measurable lesion; Eastern Cooperative Oncology Group performance status 0-1; controlled hypertension; and no previous systemic therapy for RCC.

For the dose-finding phase, the researchers enrolled 11 patients between September 23, 2014, and March 25, 2015 (ClinicalTrials.gov Identifier: NCT02133742), then an additional 41 patients were enrolled between June 3, 2015, and October 13, 2015, for the dose-expansion phase.

Patients received axitinib 5 mg orally twice daily with pembrolizumab 2 mg/kg IV every 3 weeks. Assessments for safety were conducted in all patients after having received at least 1 dose of axitinib or pembrolizumab. Assessments for antitumor activity were conducted in patients who received the study treatment and had an adequate baseline tumor assessment. Investigator-assessed dose-limiting toxicity during the first 2 cycles (6 weeks) — the primary end point — was used to estimate the maximum tolerated dose and recommended phase 2 dose.

Patients in both phases were analyzed together. Among the 11 patients in the 6-week dose-finding phase, 3 dose-limiting toxicities were reported (transient ischemic attack in 1 patient, treatment-related toxicity after receiving less than 75% of the planned axitinib dose in 2 patients). Twenty-five patients were still receiving the study treatment at the data cutoff date (March 31, 2017).

More in Kidney Cancer

An evaluation of patients with clear cell renal cell carcinoma revealed greater risk of death for female patients with high relative visceral fat area (rVFA), highlighting the significance of metabolic ...